Abstract
Healthy aging is accompanied by progressive decline in cognitive performance and concomitant changes in brain structure and functional architecture. Age-accompanied alterations in brain function have been characterized on a network level as weaker functional connections within brain networks along with stronger interactions between networks. This phenomenon has been described as age-related differences in functional network segregation. It has been suggested that functional networks related to associative processes are particularly sensitive to age-related deterioration in segregation, possibly related to cognitive decline in aging. However, there have been only a few longitudinal studies with inconclusive results. Here, we used a large longitudinal sample of 284 participants between 25 to 80 years of age at baseline, with cognitive and neuroimaging data collected at up to three time points over a 10-year period. We investigated age-related changes in functional segregation among two large-scale systems comprising associative and sensorimotor-related resting-state networks. We found that functional segregation of associative systems declines in aging with exacerbated deterioration from the late fifties. Changes in associative segregation were positively associated with changes in global cognitive ability, suggesting that decreased segregation has negative consequences for domain-general cognitive functions. Age-related changes in system segregation were partly accounted for by changes in white matter integrity, but white matter integrity only weakly influenced the association between segregation and cognition. Together, these novel findings suggest a cascade where reduced white-matter integrity leads to less distinctive functional systems which in turn contributes to cognitive decline in aging.
Highlights
We found that the rate of change in associative system segregation was positively associated with the rate of change in general cognitive function (n = 161, r = 0.18, t158 = 2.21, p = 0.028; Fig. 2B), such that greater decline in segregation was associated with worsened cognitive performance over time, independent of participants’ age
Our results showed partial contributions of white matter integrity to changes in functional segregation, it is important to note that neurochemical factors, such as glucose energy utilization, dopamine, and noradrenaline and their alterations in aging may contribute to age-related changes in functional segregation
The results in the current study indicate that functional segregation declines over a period up to 10 years, with divergent trajectories of change between associative and sensorimotor-related systems
Summary
Healthy aging is accompanied by progressive decline of cognitive performance (Nyberg et al, 2003a; Nilsson et al, 2004; Gorbach et al, 2017; Tucker-Drob et al, 2019) and concomitant changes in brain structure (Fjell and Walhovd, 2010; Raz et al, 2005; Salami et al, 2012a), dopaminergic neurotransmission (Bäckman et al 2010; Rieckmann et al, 2011), and metabolism (Kalpouzos et al, 2009; Camandola and Mattson, 2017). Age-related disruptions in functional brain architecture may have detrimental consequences for cognitive function, as maintenance of segregated systems is important for optimal brain function and metabolic efficiency (Van den Heuvel and Sporns, 2011; Bullmore and Sporns, 2012; Wig, 2017) Along these lines, previous studies have reported a positive association between particular cognitive processes and the degree of system segregation at different levels of organization (Chan et al, 2014; Gu et al, 2015; Cohen and D’Esposito, 2016; Grady et al, 2016; Yue et al, 2017; Nashiro et al, 2017). Cross-sectional estimates of age-related changes may deviate from their longitudinal counterparts (e.g., Nyberg et al, 2010), calling for further examination of changes in functional segregation in relation to cognitive decline in a longitudinal setting
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